CoVPN 3005 - Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older

FOA：PA-20 - 272：现有NIH赠款和合作协议的行政补充 活动代码/奖项：UM1/A1068614 - 15（家长奖） ------------------------------------------------------------------------------------ 项目摘要 该提案概述了COVID-19预防网络（CoVPN）疫苗的科学议程 领导运营中心（COVID-19疫苗有效性试验的实施，名为"A 平行组、III期、多阶段、改良双盲、多组研究，以评估疗效、安全性， 两种SARS-CoV-2重组蛋白疫苗（单价和双价）的免疫原性 用于18岁及以上成年人预防COVID-19。" 随着全球COVID-19大流行，我们认识到对修饰COVID-19的疫苗的巨大需求， SARS-CoV-2感染者。为了解决这一差距，美国国立卫生研究院（NIH）迅速 CoVPN的组成，与5个NIH支持的临床试验网络合作，以创建一个增强的网络， 美国145个临床试验中心和17个国家的71个国际临床试验中心的医生-科学家，致力于 研发全球有效的SARS-CoV-2疫苗。由于其在实施全球 过去20年的艾滋病毒疫苗试验，艾滋病毒疫苗试验网络（HVTN）LOC被选为LOC 用于CoVPN疫苗试验 这项III期、多阶段、改良双盲、安慰剂对照、多组研究将测试疗效， 赛诺菲-巴斯德SARS-CoV2融合前Spike delta TM与AS03佐剂的安全性和免疫原性， 单价D614（单价疫苗）& SARS-CoV2融合前Spike delta TM + AS03佐剂，二价 D614/B.1.351（二价疫苗），用于18岁及以上成人的COVID-19疾病。参与者 将从美国和全球的临床试验中心招募，使用数据分析来瞄准高风险 具有不同种族和族裔背景的个人。 参与者将接受SARS-CoV-2感染的症状筛查，如果他们被感染， 通过频繁的临床检查和远程监测生命体征进行监测。受感染的人， 中重度COVID-19患者将被转诊住院。所有试验终点分析将使用 用于诊断和免疫监测的合格和经验证的测定。 本研究的具体目的是评估研究性CoV2 preS dTM重组体的临床疗效 在初治成人中用AS03佐剂的蛋白质-单价和二价（"研究疫苗"），用于预防 第二次注射后> 14天出现症状性COVID-19;评估研究的安全性 在整个研究期间，与安慰剂相比，疫苗;在SARS-CoV-2初治的参与者中， CoV2 preS dTM-AS03疫苗预防> 14天后发生以下事件的临床功效 第二次注射：预防SARS-CoV-2感染，预防重症COVID-19;描述 非SARS-CoV-2初治成人中症状性COVID-19发作的疾病频率和谱， 每个研究小组。 这项效力试验将告诉我们两种重组疫苗的能力，它们针对两种最常见的 常见的SARS-CoV-2变异体，以诱导强适应性保护反应。在Novavax疫苗之后， 是第二个大规模的重组蛋白疫苗进行有效性测试，这是第一次使用 包括B.1.351变异体在内的二价疫苗。如果成功，这将是一种重要的疫苗， 迅速扩大规模并部署到世界各地。这项试验的结果将用于评估注册 这一疫苗产品，也将提供重要信息，告知后代的COVID-19 疫苗。

FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines.